Nestin-lineage cells contribute to the microvasculature but not endocrine cells of the islet

Nestin-lineage cells contribute to the microvasculature but not endocrine cells of the islet
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DOI:
10.2337/diabetes.52.10.2503
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发表时间:
2003-10-01
期刊:
影响因子:
7.7
通讯作者:
Burant, CF
Burant, CF
中科院分区:
医学1区
文献类型:
--
作者:
Treutelaar, MK;Skidmore, JM;Burant, CF

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为了阐明表达胰腺的神经干细胞标记巢和内分泌细胞的细胞之间的谱系关系,我们分析了携带巢蛋白启动子/增强子驱动的Cre-Recombinase(Nestin-cre)和C57BL/6JJBL/6JJ的小鼠之间的杂交后代-gtrosa26(TM1SOR)小鼠,携带loxp beta-galactosidase基因的小鼠(Rosa26)。在Nestin-Cre(+/Tg); R26R(1OXP/+)胚胎中,与胰腺间充质中的巢蛋白阳性细胞相关检测CRE-异构酶与某些Nestin阳性细胞内膜血管通道。在产后小鼠中,胰腺β-半乳糖苷酶的表达仅限于胰岛的血管内皮细胞,而动脉的肌科动脉中与内源性巢蛋白表达相同的细胞中的细胞子集。小鼠胰管的离体外植体增长了巢蛋白和β-半乳糖苷酶的浓厚培养物,在体外表现出重组。这些培养物可以分化为复杂的刻板印象结构,这些结构包含巢蛋白和表达胰岛素的细胞。 Nestin-Cre(+/Tg); R26R(1OXP/+)衍生的管道培养物表明胰岛素阳性细胞对β-半乳糖苷酶为阴性。这些结果表明,体内和体外胰腺内分泌细胞都独立于Nestin阳性前体出现。 Nestin阳性细胞群和与内分泌细胞的密切相关的表观血管性质表明,Nestin阳性细胞在胰岛的生长和维持中起着重要作用。
To clarify the lineage relationship between cells that express the neural stem cell marker nestin and endocrine cells of the pancreas, we analyzed offspring of a cross between mice carrying a nestin promoter/enhancer-driven cre-recombinase (Nestin-cre) and C57BL/6J-Gtrosa26(tm1Sor) mice that carry a loxP-disrupted beta-galactosidase gene (Rosa26). In nestin-cre(+/tg);R26R(1oxP/+) embryos, cre-recombinase was detected in association with nestin-positive cells in the pancreatic mesenchyme with some of the nestin-positive cells lining vascular channels. In postnatal mice, pancreatic beta-galactosidase expression was restricted to vascular endothelial cells of the islet and a subset of cells in the muscularis of arteries in a distribution identical to endogenous nestin expression. Ex vivo explants of mouse pancreatic ducts grew dense cultures that costained for nestin and beta-galactosidase, demonstrating recombination in vitro. The cultures could be differentiated into complex stereotypic structures that contain nestin and insulin-expressing cells. Nestin-cre(+/tg);R26R(1oxP/+)-derived duct cultures showed that insulin-positive cells were negative for beta-galactosidase. These results indicate that both in vivo and in vitro pancreatic endocrine cells arise independently of nestin-positive precursors. The apparent vascular nature of the nestin-positive cell population and the close association with endocrine cells suggest that nestin-positive cells play an important role in the growth and maintenance of the islet.